Journal of Thoracic Oncology:
A Patient With BRAF V600E Lung Adenocarcinoma Responding to Vemurafenib
Gautschi, Oliver MD*; Pauli, Chantal MD†; Strobel, Klaus MD‡; Hirschmann, Astrid†; Printzen, Gert MD§; Aebi, Stefan MD*; Diebold, Joachim MD†
Departments of *Medicine, †Pathology, ‡Nuclear Medicine, and §Laboratory Medicine, Luzerner Kantonsspital, Luzern, Switzerland.
Disclosure: The authors declare no conflict of interest.
Address for correspondence: Oliver Gautschi, MD, Medical Oncology, Luzerner Kantonsspital, 6000 Luzern, Switzerland. E-mail: firstname.lastname@example.org
Vemurafenib is active against metastatic melanoma with BRAF V600E mutation.1,2 BRAF mutations were reported in 3% to 5% of non–small-cell lung cancers (NSCLC) by the US Lung Cancer Mutation Consortium and by Italian investigators.3,4 In vitro, MEK inhibition in lung cancer cell lines with V600E induced apoptosis, but clinical experience with drugs targeting the RAS/RAF/MEK pathway in V600E-NSCLC is limited.5
An 80-year-old man was admitted to our hospital with a history of shortness of breath and hoarseness. He was a former smoker and received torasemide (a diuretic) for hypertensive heart disease. Computed tomography (CT) scan showed a central tumor in the left lung, mediastinal lymph node metastases, and left pleural effusion (Fig. 1A). Drainage of pleural and pericardial effusion was performed, followed by pericardial instillation of bleomycin and talc slurry of the left pleura. Cytology revealed thyroid transcription factor-1 positive cancer cells, consistent with the diagnosis of NSCLC stage M1a (Fig. 2A). Polymerase chain reaction and direct sequencing showed BRAF V600E mutation (Fig. 2B). Sequencing of epidermal growth factor receptor exon 18 to 21, KRAS exon 2, and human epidermal growth factor receptor 2 exon 19 to 20 was negative. Anaplastic lymphoma kinase fluorescence in situ hybridization was also negative. The performance status was 4, the prognosis was very poor, chemotherapy was not recommended, and the patient was ineligible for a clinical trial with an MEK inhibitor. After exclusion of contraindications, the patient was offered vemurafenib off-label use. Pretreatment fluorodeoxyglucose–positron emission tomography/CT was performed (Fig. 1B), vemurafenib was initiated at the regular dose of 960 mg bid, and the patient left the hospital in a stable condition supported by family and professional home care. After 1 week of vemurafenib, his clinical and laboratory parameters were stable, and he decided to continue. After 2 weeks, follow-up fluorodeoxyglucose–positron emission tomography/CT showed good metabolic response (Fig. 1C). The condition of the patient was stable, and he remained on treatment. Three days later, he was admitted to the emergency room with worsening of dyspnoe, and clinical examination revealed progressive bilateral pleural effusions. Vemurafenib was stopped, the patient received terminal care, and died. Autopsy showed massive bilateral pleural effusions, global heart dilatation, and severe biventricular hypertrophy. Cytology showed near complete absence of cancer cells in pleural fluid, and histology showed massive tumor regression with fibrosis and few residual cancer cell islets (Fig. 2C, D). N-terminal B-type natriuretic peptide in archived pretreatment serum was 1880 pg/ml, consistent with chronic cardiac failure. To the best of our knowledge, this is the first report of a patient with V600E-NSCLC responding to vemurafenib. Unfortunately, the patient did not obtain clinical benefit because he died from a comorbidity without evidence of drug toxicity. We hope that this report may encourage further study on vemurafenib in V600E-NSCLC.
We thank the patient for consenting before his death to release medical information and images. We thank Drs. Schwizer, Schlaepfer, and Allelein from our institution for collaboration, and Dr. Juerg Aebi from Roche Switzerland for providing vemurafenib.
1. Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366:707–714
2. Chapman PB, Hauschild A, Robert C, et al.BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–2516
3. Kris MG, Johnson BE, Kwiatkowski DJ, et al. Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: The NCI’s Lung Cancer Mutation Consortium (LCMC). J Clin Oncol. 2011;29(Suppl) abstr CRA7506
4. Marchetti A, Felicioni L, Malatesta S, et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol. 2011;29:3574–3579
5. Pratilas CA, Hanrahan AJ, Halilovic E, et al. Genetic predictors of MEK dependence in non-small cell lung cancer. Cancer Res. 2008;68:9375–9383
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